Zn2+ blocks the NMDA- and Ca2+ -triggered postexposure current ipe in hippocampal pyramidal cells.
Whole cell voltage-clamp recordings from acutely isolated hippocampal CA1 pyramidal cells from adult guinea pigs were used to evaluate divalent cations as possible blockers of the postexposure current (Ipe). Ipe is a cation current that is triggered by the rise in intracellular Ca2+ concentration that occurs after the application of a toxic level of N-methyl-D-aspartate (NMDA). Once triggered, Ipe continues to grow until death of the neuron occurs. Ipe may be a critical link between transient NMDA exposure and cell death. Ipe was blocked by micromolar concentrations of Zn2+. The Zn2+ effect had an IC50 of 64 microM and saturated at 500 microM. Prolonged Zn2+ block of Ipe revealed that the maintenance of a steady Ipe is not dependent on Ipe-mediated Ca2+ influx but that the continuous growth in Ipe is dependent on Ipe-mediated Ca2+ influx. The availability of an effective blocker of Ipe should facilitate the investigation of the intracellular activation pathway of Ipe and the role of Ipe in neuronal death.
Chen
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QX
Department of Pharmacology, State University of New York Health Science Center, Brooklyn, New York 11203, USA.
Perkins
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KL
Wong
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RK
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D016923:Cell Death; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006168:Guinea Pigs; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D015032:Zinc / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016202:N-Methylaspartate; D015032:Zinc; D002118:Calcium